MicroRNA-939-5p directly targets IGF-1R to inhibit the aggressive phenotypes of osteosarcoma through deactivating the PI3K/Akt pathway.

The dysregulation of microRNA‑939‑5p (miR‑939) is involved in the development of multiple types of human cancer. However, the expression and roles of miR‑939 in osteosarcoma (OS) have yet to be clarified. The expression level of miR‑939 in OS was measured using reverse transcription quantitative polymerase chain reaction (RT‑qPCR). A Cell Counting Kit‑8 assay, flow cytometry analysis, Transwell migration and invasion assays, and a tumor xenograft assay were employed to explore the effects of miR‑939 in OS cells. Bioinformatics analysis, RT‑qPCR, western blot analysis and luciferase reporter assays were performed to explore its underlying mechanism. Expression of miR‑939 was decreased in both OS tissues and cell lines. The decreased miR‑939 expression was notably correlated with clinical stage and distant metastasis in patients with OS, where low miR‑939 levels were correlated with lower overall survival. miR‑939 overexpression decreased OS cell proliferation, migration and invasion in vitro; induced cell apoptosis, and impaired tumor growth in vivo. Mechanistically, insulin‑like growth factor 1 receptor (IGF‑1R) was characterized as direct target gene of miR‑939 in OS. The tumor‑suppressing effects of miR‑939 in OS cells were imitated by IGF‑1R knockdown. In addition, exogenous IGF‑1R expression abolished the tumor suppressive roles of miR‑939 in OS cells. miR‑939 was implicated in the deactivation of the PI3K/Akt pathway in OS in vitro and in vivo through regulating IGF‑1R expression. The present study demonstrated that miR‑939 exerted tumor‑suppressing roles in the malignancy of OS cells by directly targeting IGF‑1R and inactivating the PI3K/AKT pathway. Therefore, this miRNA may be a promising target for anticancer therapy in patients with OS.

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